title: Negative regulation of RIG-I-mediated antiviral signaling by TRK-fused gene (TFG) protein.
abstract: RIG-I (retinoic acid inducible gene I)-mediated antiviral signaling serves as the first line of defense against viral infection. Upon detection of viral RNA, RIG-I undergoes TRIM25 (tripartite motif protein 25)-mediated K63-linked ubiquitination, leading to type I interferon (IFN) production. In this study, we demonstrate that TRK-fused gene (TFG) protein, previously identified as a TRIM25-interacting protein, binds TRIM25 upon virus infection and negatively regulates RIG-I-mediated type-I IFN signaling. RIG-I-mediated IFN production and nuclear factor (NF)-κB signaling pathways were upregulated by the suppression of TFG expression. Furthermore, vesicular stomatitis virus (VSV) replication was significantly inhibited by small inhibitory hairpin RNA (shRNA)-mediated knockdown of TFG, supporting the suppressive role of TFG in RIG-I-mediated antiviral signaling. Interestingly, suppression of TFG expression increased not only RIG-I-mediated signaling but also MAVS (mitochondrial antiviral signaling protein)-induced signaling, suggesting that TFG plays a pivotal role in negative regulation of RNA-sensing, RIG-I-like receptor (RLR) family signaling pathways.
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Na-Rae
authors.initials: NR
authors.lastname: Lee
authors.forename: Han-Bo
authors.initials: HB
authors.lastname: Shin
authors.forename: Hye-In
authors.initials: HI
authors.lastname: Kim
authors.forename: Myung-Soo
authors.initials: MS
authors.lastname: Choi
authors.forename: Kyung-Soo
authors.initials: KS
authors.lastname: Inn
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism*; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D016899:Interferon-beta / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D011971:Receptors, Immunologic; D029082:Sendai virus / Q000502:physiology; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D014721:Vesicular stomatitis Indiana virus / Q000502:physiology; D014779:Virus Replication; D033921:Vesicular Transport Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000998:Antiviral Agents; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D049452:Green Fluorescent Proteins; D016899:Interferon-beta; D011506:Proteins; D011971:Receptors, Immunologic; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; C505371:MAVS protein, human; C096163:TFG protein, human; D033921:Vesicular Transport Proteins; C485184:enhanced green fluorescent protein; C084523:TRIM25 protein, human; C452820:RIGI protein, human
keywords: Antiviral signaling; Interferon; RIG-I; TFG; TRIM25; TRK-fused gene protein